tbuckley/cabot-search huggingface dataset:
Abstract 12772: Transcatheter Aortic Valve Replacement Improves Functional and Quality Of Life Outcomes in Patients With Low Gradient Aortic Stenosis
Authors: Kelsey Danley, Margaret Brandon, Caleb Chiang, Shengyuan Luo, Laith A Derbas, Fareed M Collado, Clifford J Kavinsky, Hussam S Suradi
Journal: Circulation (2022)

Introduction: Aortic stenosis (AS) is the most common valvular disease, and severe disease can significantly impact morbidity. Less data exists examining the functional and quality of life (QOL) effects of transcatheter aortic valve replacement (TAVR) in patients with severe low-gradient AS in both low-flow and normal-flow states. Hypothesis: Patients with symptomatic, severe, low-gradient AS would have improvements in functional and QOL outcomes at 30-days and 1-year following TAVR procedures. Methods: A single center, retrospective study examined symptomatic, severe, low-gradient AS variants. These had an aortic valve area of ≤1.0 cm 2 , mean transvalvular gradient &lt;40 mmHg, and peak aortic valve velocity of &lt;4 m/s. Classical low-flow low-gradient (CLFLG) AS was defined as a left ventricular ejection fraction (LVEF) &lt;50%. CLFLG group underwent dobutamine stress echo to assess AS severity (Stage D2). Paradoxical low-flow low-gradient (PLFLG) AS was defined as LVEF ≥50% and a stroke volume index (SVi) ≤35mL/m 2 (Stage D3). Normal-flow low-gradient (NFLG) AS was defined as LVEF ≥50% and SVi &gt;35mL/m 2 (Stage D4). The primary outcome was change in New York Heart Association (NYHA) classification and a 12-item Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS) at 30-days and 1-year following TAVR. Results: A total of 191 patients were included for analysis: 46 CLFLG, 83 PLFLG, and 62 NFLG AS. At baseline, 130 (68%) had NYHA class III or IV symptoms. Mean baseline KCCQ-OS for all groups was 38±23 (Figure 1). The mean KCCQ-OS at 30-days and 1 year were 62±22 and 68±20. There were no significant differences in KCCQ-OS between the groups at 30-days and 1-year. Following TAVR, 92% and 88% of the cohort had NYHA class I or II symptoms at 30-days and 1 year. Conclusions: Patients with symptomatic, severe low-gradient AS had significant and sustained improvements in their functional and QOL metrics at 30-days and 1-year following TAVR procedures regardless of flow-state.
Abstract 13349: Inclusion and Enrollment of Women and Minorities in Left Atrial Appendage Occlusion Clinical Trials: A Meta-Analysis
Authors: Kavin Sundaram, Syed Rafay Ali Sabzwari, Ryan G Aleong, Alexis Tumolo, Michael Rosenberg, Matthew Zipse, Wendy Tzou, Lohit Garg
Journal: Circulation (2022)

Introduction: Retrospective studies suggest that women undergoing left atrial appendage occlusion may have worse outcomes and population-based studies suggest racial variations in appendage anatomy and risk of stroke. Hypothesis: Randomized controlled trials of LAAO for atrial fibrillation will have low rates of inclusion of women and racial minorities. Methods: Databases were queried for all randomized clinical trials of LAAO from inception until May 2022 and included in the analysis (Figure 1) . Results: The search strategy identified 10 trials for inclusion in the study. Most studies reported rates of participation of women (9/10, 90 percent Figure 2a ). The inclusion of women in these trials were low and constituted 34% of included patients (29-42%) with high heterogeneity ( Figure 3a). Among these reports, only two studies (2/10, 20 percent, Figure 2b ) reported details of the race and ethnicity of participants and 1031 / 1114 (93%) were Caucasians. Meta-analysis showed low heterogeneity Figure 3b). Conclusions: In trials of LAAO for atrial fibrillation, rates of inclusion of women remain low relative to population prevalence. Reporting of participation of ethnic minorities also remains low. Improvement in these areas in future studies may help support the generalizability of the existing literature.
Abstract 13141: Age of Onset and Clinical Outcomes in <i>RBM20</i> -Mediated Arrhythmogenic Dilated Cardiomyopathy
Authors: Ramin Garmany, Andrew S Tseng, Naveen L Pereira, Ciorsti MacIntyre, Jay W Schneider, Michael J Ackerman, John Giudicessi
Journal: Circulation (2022)

Introduction: Pathogenic loss-of-function variants in the RBM20 -encoded RNA-binding motif 20 splicing regulator cause a severe form of arrhythmogenic dilated cardiomyopathy (DCM). Erroneous splicing of TTN -encoded titin contributes to the pathogenesis of RBM20 -mediated disease. However, studies exploring the clinical course of RBM20 -mediated arrhythmogenic DCM alone or in comparison to TTN -mediated DCM, the most common familial cause of DCM, are lacking. Methods: The Mayo Clinic Genetic Arrhythmogenic Cardiomyopathy Registry (n=391) was used to identify all patients with a pathogenic/likely pathogenic (P/LP) variant in either RBM20 or TTN . For the purposes of this study, a ventricular arrhythmia (VA) event was defined as sudden cardiac arrest, sustained ventricular arrhythmia, or an appropriate ICD shock and an advanced heart failure (AHF) event was defined as ventricular assist device implantation or heart transplantation. Results: Overall, 40 patients with a P/LP variant in RBM20 (50% female) and 70 patients with a P/LP variant in TTN (43% female) were identified. The prevalence of a cardiac phenotype in patients with RBM20- and TTN -mediated disease was 88% and 83%, respectively. RBM20 patients were more likely to have a family history of sudden cardiac arrest (78% vs 34%; p &lt; 0.0001) and cardiomyopathy (90% vs 61%; p=0.001). No difference in rate of ICD implantation (35% versus 33%) was observed. Interestingly, the prevalence of AHF events (10% vs 6%; p=0.5) and VA events (28% vs 24%; p=0.7) was similar between RBM20 - and TTN -positive patients. However, RBM20 patients were younger than TTN patients at the time of their event (37 ± 18 years vs 50 ± 17; p=0.0004). Time-to-event analysis showed RBM20 patients had an earlier time to AHF event (p=0.05) and time to VA event (p=0.03) than TTN patients. The mean age for AHF events was 25 years for RBM20 patients (N=4) and 47 years for TTN patients (N=4). The mean age for VA events was 29 years for RBM20 patients (N=10) and 42 years for TTN patients (N=14). Conclusions: RBM20 -mediated arrhythmogenic DCM represents a highly penetrant genetic heart disease with potentially life-threatening VAs and end stage heart failure manifestations occurring at a significantly younger age in comparison to TTN -mediated DCM.
Abstract 13538: Associations Between Circulating Liver Enzymes and Platelet Reactivity
Authors: Bongani Nkambule, Melissa V Chan, Amber Lachapelle, Joseph Grech, Florian Thibord, Jason Cuhna, Robin Pashek, Ming-Huei Chen, Andrew D Johnson
Journal: Circulation (2022)

Introduction: The liver plays an essential role in thrombopoiesis and coagulation, and circulating liver enzymes are associated with altered platelet counts. However, the role of liver enzymes in the modulation of platelet reactivity remains unclear. Methods: A total of 3,429 Framingham Heart Study participants were included in this study. Platelet reactivity to 8 agonists, including adenosine diphosphate (ADP), thromboxane A 2 mimetic (U46619) and arachidonic acid (AA), was measured using light transmission aggregometry (LTA), Multiplate impedance aggregometry and Optimul aggregometry. Platelet counts and platelet-red blood cell aggregates were enumerated using flow cytometry. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. Associations of platelet reactivity phenotypes with liver circulating liver enzyme levels analyzed using linear mixed-effects models and adjusted for sex, age, relatedness, smoking, aspirin-, and statin-use. To correct for multiple testing, a Bonferroni-correction threshold of P&lt;0.0011 was used to account for multiple comparisons. Results: Higher ALT levels were associated with platelet disaggregation in LTA to ADP (β=0.056, SE=0.02, P=3.54E-04), and with decreased platelet reactivity in response to U46619 in Optimul (EC 50 : β=0.064, SE=0.019, P=7.65E-04). Interestingly, higher AST levels were associated with decreased platelet counts (β=-0.082, SE=0.019, P=1.04E-05), platelet reactivity to U46619 (β=-0.069, SE=0.018, P=1.04E-04) and AA (β=-0.047, SE=0.013, P=3.12E-04), and circulating platelet-red blood cell aggregates (β=-0.062, SE=0.018, P=9.54E-04). Conclusion: Our findings suggest that ALT levels could alter primary platelet aggregation. AST may indirectly modulate platelet counts. In addition, lower AST levels may contribute to platelet hyperresponsiveness. Lastly, ALT and AST levels may have antagonistic effects on the formation of platelet and red blood cell aggregates, which may indirectly influence platelet margination within vessels. Additional studies are underway to examine whether liver fat, a marker of fibrosis associated with cardiovascular disease, is also associated with altered platelet function.
Abstract 14054: Monocyte Vascular Endothelial Growth Factor Receptor-1 Signaling in Peripheral Artery Disease
Authors: Abdelrahman A Zaied, Lauren Brewer, Sholeh Rezaee, Edie Threlkeld, Silvia Leanhart, Adeleigh Hamilton, Brian H Annex
Journal: Circulation (2022)

Introduction: Peripheral artery disease (PAD) is caused by atherosclerosis of large arteries of the leg(s). Beyond complications from poor perfusion to the legs, patients with PAD suffer higher than expected rates of heart attack and strokes. Monocytes are subdivided into three subtypes: CD14++CD16- (classical), CD14+CD16+ (intermediate), and CD14-CD16+ (non-classical). The intermediate monocyte subtype is linked to PAD. Vascular Endothelial Growth Factor receptor (VEGFR)-1 is a member of tyrosine kinase family that is expressed in monocytes and has high affinity for the VEGF-A ligand. Recent studies showed that inhibition of VEGFR1/STAT-3 signaling decreases angiogenesis in PAD. We hypothesized that in patients with PAD, intermediate monocytes would have less VEGFR1/STAT3 activation than controls. Methods: Blood samples were collected from PAD patients (n=11) and risk factor closely matched controls (n=17). PBMCs were isolated by gradient centrifugation. By flow cytometry, gating strategy on monocytes was done by excluding granulocytes (CD66b), B and T lymphocytes (CD3,CD19), and natural killer cells (CD56). Next, monocytes were subdivided into three populations (intermediate, classical, and non-classical) by gating according to their CD14/CD16 expression. Within each population, levels of p(Y1333)VEGFR1, VEGFR1, pSTAT3, and STAT3 were determined. Results: Data from flow cytometry analysis showed a significant increase in the intermediate monocyte population in PAD vs control (~1.5-fold change; p=0.01). However, there was no significant difference in the non-classical or classical monocytes between PAD and control. Within the intermediate monocytes, P(Y1333) VEGFR1/VEGFR1 was decreased (~2-fold change) and pSTAT3/STAT3 was significantly decreased (~2-fold change) in PAD vs control. In both the non-classical and classical monocytes, there was no significant difference in either phosphorylated receptor between PAD and control. Conclusions: The data confirm the intermediate monocyte is associated with PAD and suggest that VEGFR1/STAT3 signaling is decreased in intermediate monocytes in PAD vs control. Understanding the mechanism of VEGFR1 activation may prove to be a promising therapeutic target for patients with PAD.
Abstract 12899: A Patient-Specific Fluid-Structure Interaction-Based Approach to Improve Surgical Predictability in Bicuspid Aortic Valve Patients
Authors: Charles Wanna, Arun Kolanjiyil, Krishnan B Chandran, Hyunggun Kim, Danai Kitkungvan, Kathryn J Grande Allen, Danny Ramzy, David D McPherson, Siddharth K Prakash, Vijay Govindarajan
Journal: Circulation (2022)

Introduction: BAV is the most common congenital heart defect affecting ~1.4% of the population. It also brings with it an increased risk of aortopathy, including coarctation, aneurysm, dissection, and accelerated calcification with either stenosis or aortic insufficiency. Quantifying BAV function, altered blood flow, and corresponding hemodynamic forces and their impact on accelerated BAV deterioration improves BAV diagnosis. Predicting how these parameters improve post-interventions may improve surgical predictability and long-term outcome. Methods: A patient-specific modeling protocol based on MRI-based patient data and strongly coupled fluid-structure interaction (FSI) technique was developed to evaluate BAV. Flow via left ventricle, BAV, ascending and descending aorta (Fig A-B) was simulated to obtain biomechanical insights near valve vicinity and study its effects downstream. Diseased anatomy was simulated, and biomechanics compared with virtual interventions that included 1) surgical aortic valve replacement (SAVR), 2) valve sparing root replacement (VSRR) with a sinus graft, and 3) VSRR without sinus graft (Fig C). Results: Our model predictions showed that viscous dissipation (or energy loss) was the greatest in the diseased BAV indicating a high energy loss that substantially reduced post-virtual interventions. Specifically, energy loss reduced by 2.55-, 1.65-, 2.52- folds for SAVR, VSRR-sinus, and VSRR+sinus respectively at peak-systole (Fig. E-H). Interestingly, while SAVR produced the largest orifice area (OA), OA of BAV marginally reduced post VSRR during peak-systole (Fig. I) Conclusions: These studies provide insights into BAV dynamics and may help determine the optimal interventions for a patient. These insights may help improve diagnosis and surgical predictability, optimize treatment, and help with clinical decision making for BAV patients at risk.
Abstract 14417: Implications of Atrial Fibrillation on Clinical Outcomes of Patients With Hypertrophic Obstructive Cardiomyopathy
Authors: Irfan Shafi, Abdalaziz Awadelkarim, Rashid Alhusain, Hersimren Minhas, Nasser Lakkis
Journal: Circulation (2022)

Introduction: Atrial fibrillation is a comorbidity often seen in patients with hypertrophic cardiomyopathy (HCM); however, contemporary data on its prevalence and clinical implications in the obstructive variant of HCM is scarce. Hypothesis: We sought to study the outcomes and implications of atrial fibrillation among patients hospitalized with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Patients with a principal discharge diagnosis of HOCM between 2016 and 2019 were identified in the National Readmissions Database. Among those, patients with and without a diagnosis of atrial fibrillation were categorized. HOCM hospitalizations with atrial fibrillation were matched 1:1 fashion to HOCM without atrial fibrillation. Results: Of the 40,516 HOCM hospitalizations, 14,637 (36.12%) had a secondary diagnosis of atrial fibrillation. Propensity score-matched comparison between HOCM with and without atrial fibrillation (Figure 1) showed higher cardiogenic shock (2.69% vs. 1.98%, p-value &lt;0.01), and acute stroke (3.85% vs 2.91%, p-value &lt;0.01) as compared with HFpEF without atrial fibrillation (Table 1). Total charges were higher in HOCM with atrial fibrillation compared to patients without atrial fibrillation ($ ($86,392.6 vs. $83,762.21). The 30 days all-cause readmission rate among patients admitted with HOCM with AF was higher than those without AF (15.91% vs 14.80, p-value &lt;0.01). Conclusions: In patients with HOCM presence of atrial fibrillation was associated with higher cardiogenic shock and acute stroke.
Abstract 14413: Possible Antibody Mediated Cardiac Rejection After Combined Heart-Kidney Transplant in a Sensitized Patient Associated to COVID-19 Pneumonia
Authors: Josefina Castillo, Ana Mireya Ortiz, Jorge Jalil, Douglas Greig, Samuel Córdova, Rodrigo Fernández, Pablo Castro
Journal: Circulation (2022)

Background: Antibody mediated rejection (AMR) starts with the appearance of donor-specific antibodies (DSA), followed by graft injury that may be subclinical and can progress to cardiac allograft vasculopathy (CAV) and chronic graft dysfunction. Case report A 48-year-old man with a past medical history of right nephrectomy due to congenital renal atrophy and dilated cardiomyopathy required heart transplantation at age 31, presented an episode of AMR grade 2 ten years post-transplant developing CAV with graft loss and end-stage renal disease. He was listed for a combined heart-kidney transplant. His panel reactive antibody (PRA) level was 40%, requiring desensitization therapy (plasmapheresis, intravenous gamma globulin and rituximab). At age 44, he received a heart-kidney transplant. Methylprednisolone and rabbit antithymocyte globulin were used for induction and desensitization therapy with plasmapheresis and intravenous gamma globulin at months 0-3-6-12 was continued. Maintenance immunosuppression therapy continued with tacrolimus, mycophenolic acid and prednisone. During follow-up persistent circulating DSA anti-class II HLA were detected and PRA reached 80%. He was admitted with a multifocal COVID-19 pneumonia. He had received 4 doses of the messenger RNA vaccine BNT162b2. Dexamethasone was started and mycophenolic acid was discontinued for 14 days. He did not need mechanical ventilation. Echocardiogram revealed marked concentric LVH, LVEF = 60%, grade II diastolic dysfunction and reduced global longitudinal strain (-7,6%). Pro-BNP was 962 pg/ml, and Troponin T 100 pg/ml. Endomyocardial biopsy showed no signs of cellular rejection nor capillary injury. Immunopathologic findings were negative. Coronary angiogram showed no significant lesions. AMR was suspected, the patient was treated with methylprednisolone, plasmapheresis and intravenous gamma globulin. Clinical response was satisfactory, and he was discharged in functional class I (NYHA). Conclusions Although both histological and immunopathologic studies were negative, clinical suspicion for AMR in a highly sensitized patient prevailed in the context of a recent infectious intercurrence. Other diagnosis cannot be completely ruled out in this clinical scenario.
Abstract 14398: Novel Cardiac Electrical Activation Parameter Associated With CRT Response
Authors: Kenneth C Bilchick, Derek Bivona, Frances Morales, Puneet Sharma, Andrew Darby, Rohit Malhotra, Oliver Monfredi, Pamela K Mason, J M Mangrum, Pim Oomen
Journal: Circulation (2022)

Introduction: Simultaneous assessment of cardiac electrical activation and left ventricular (LV) function could identify optimal cardiac resynchronization therapy (CRT) pacing strategies, leading to improved CRT response and outcomes. Hypothesis: Changes in three-dimensional (3D) cardiac electrical activation timing correlate with LV function. Methods: 3D cardiac electrical activation maps from the CardioInsight 252-electrode mapping vest (Medtronic) and cardiac ultrasound images were acquired during and 6 months after CRT defibrillator implantation. Maps were acquired for intrinsic electrical activation and three CRT pacing configurations: synchronized LV pacing, right ventricular (RV) pacing, and biventricular (BIV) pacing. Three novel electrical activation parameters were calculated: LV80, RV80, and BIV80, defined as the time at which 80% of the LV, RV, or both ventricles, respectively, were electrically activated. Results: In 30 CRT patients (65.6 ± 11.3 years old, 36.7% female, 43.3% with LV scar, 57% with left bundle branch block [LBBB], and 43% with right bundle branch block [RBBB]), simultaneous measurements of electrical activation and LV function were obtained. Figure panels A and B show representative plots of the proportion of the LV and RV activated versus time within the QRS for a patient with LBBB. In this patient, BIV pacing improved the LV80 but worsened the RV80 compared with the intrinsic rhythm, consistent with a discordant effect on ventricular function. Panel C shows that synchronized LV pacing has a more unfavorable effect on RV activation than BIV pacing in this patient. In the entire cohort, the BIV80 was significantly associated with the change in LVESVI six months after CRT (p&lt;0.05) (panel D). Conclusion: A novel measurement of 3D cardiac electrical activation demonstrates the effects of different CRT pacing strategies on LV and RV function and predicts LV functional improvement after CRT.
Abstract 14809: Longitudinal Trends in the Incidence of Covid-19 in Acute Myocardial Infarction Patients
Authors: Agam Bansal, Grant W Reed, Venu Menon, Amar Krishnaswamy, Samir R Kapadia, Umesh N Khot
Journal: Circulation (2022)

Introduction: Existing studies have reported association between acute myocardial infarction (AMI) and risk of fatal outcomes in COVID-19 patients. However, impact of Omicron COVID-19 variant on the incidence of AMI has not been studied. We aimed to ascertain longitudinal trends in incidence of COVID-19 in AMI patients with a focus on the Omicron period. Methods: We included all hospitalized patients from March 2020 to January 31 st , 2022 at all Cleveland Clinic hospitals in the U.S. who had an ICD-10 code I21 representing AMI. Data was obtained using Slicer Dicer. Primary outcome was longitudinal trends in incidence of COVID-19 in AMI patients and secondary outcome was the incidence of COVID-19 in Omicron as compared with previous waves. Hospitalisations were stratified based on following periods: stay at home order [03/2020-05/2020]; pre-vaccination [06/2020-01/2021]; post-vaccination but before delta wave [02/2021-06/2021]; delta wave [07/2021-08/2021]; and Omicron wave [12/2021-01/2022]. Trends over study period were assessed using Mann-Kendall test. Comparison of outcomes across different COVID-19 pandemic periods was performed using the chi-square test. Results: Total of 14908 hospitalizations were identified. Overall incidence rate of COVID-19 in AMI patients was 7.62% (1137/14908). From March 2020 until January 31 st , 2022, there has been a significant increase in incidence rate of COVID-19 in AMI patients from 0.83% to 29.92%, p=0.006. Incidence rate of COVID-19 in AMI during the Omicron period (25.7% (322/1252)) was significantly higher compared with the stay at home order (2.3%), pre-vaccination (8.2%), post-vaccination (4.3%), and delta wave (3.7%), p&lt;0.001. Furthermore, incidence of COVID-19 in AMI patients decreased post-vaccination period until emergence of Omicron variant. Conclusions: There has been a significant increase in the incidence of COVID-19 amongst the AMI patients which is attributed to the emergence of Omicron variant.